IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)V?6(+)?? T cells.

ABSTRACT: Interleukin-17 (IL-17)-producing ?? T (??17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4(+) and ??17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4(+) T cells direct ?? T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the V?6(+) subset of CCR2(+) ?? T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on ?? T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on V?6(+) cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.

SUBMITTER: Akitsu A 

PROVIDER: S-EPMC4521288 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature